Vasopressin is a neuroendocrine hormone secreted from the posthypophysis and, in the periphery, plays a role of maintaining the circulatory kinetics and the body fluid homeostasis mainly by the strong vasoconstricting effect through the V1 receptor and the water resorption-promoting effect in the renal collecting tubule through the V2 receptor. In addition, vasopressin possesses various physiological effects such as an effect of promoting glycogenolysis in liver, an effect of promoting the adrenocoiticotropic hormone (ACTH)-secretion from the prehypophysis or an effect of promoting the platelet agglutination.
The excess secretion of vasopressin having such effects causes various pathemas such as conjestive heart failure Pharmacological Reviews, 1991, 43:73-108), brain edema (Stroke, 1992, 23:1767-1773), arginine-vasopressin polyrrhea syndrome (Journal of Cardiovascular Pharmacology, 1986, 8:S36-S43), hepatociurhosis (Ann. Intermn Med., 1982, 96:413-417) and hypertension. Therefore, if an excellent vasopressin antagonist is developed, such antagonist may be useful as a remedy and/or a prophylactic for these diseases caused due to the excess secretion of vasopressin, for instance, heart failure, edema such as brain edema, hydroperitoneum, pneumochysis, arginine-vasopressin polyrrhea syndrome, renal failure, pancreatitis, hypertension, hepatocirrhosis, hyponatremia, hypokalemia, diabetes, circulatory disorders, Meniere's syndrome and oxytocin-related diseases; and diuretics (IGAKU NO AYUMI, 1991, 157:166). Up to now, there have been developed a variety of vasopressin-receptor antagonists for the purpose of preventing or treating vasopressin-related diseases.
In particular, the non-peptide type compound can orally be administered unlike the peptide type one. Therefore, the former would be expected to have clinical usefulness and there have been proposed various such compounds in, for instance, Japanese Un-examined Patent Publication (hereunder referred to as "J.P. KOKAI") Nos. Hei 7-2800, Hei 4-321669, Hei 4-154765, Hei 6-172317, Hei 5-132466, Hei 5-320135, Hei 6-157480, Hei 6-211800, Hei 6-16643, Hei 7-157486 and Hei 7-179430; and Published International Patent Application (hereunder referred to as "P.I.A.") Nos. WO95/03305, WO94/12476, WO94/14796 and WO94/20473. Such technical background has been disclosed in P.I.A. No. WO97/17349.
Moreover, edema is a pathema in which the extracellular fluid is excessively accumulated in external parts of blood vessels. The causes for the crisis thereof can roughly be divided into two groups, i.e., the insufficient excretion of the extracellular fluid in the exterior of the blood vessel and the excess exudation of the extracellular fluid from blood vessels. Large amounts of the fluid in the thoracic cavity or ascites would impair systemic hemodynamics (circulatory kinetics), for instance, decreases in cardiac output, the flow rate of blood in liver, and the flow rate of blood in kidney. In addition, the disease often makes it difficult for the patients suffering from the same, to take a diet due to respiratory difficulty and/or abdominal inflation. There have thus been used diuretics for relieving and treating edema.
The so-called loop diuretics presently widely used such as Furosemide (Lasix (registered trademark)) are electrolyte-discharge type diuretics which can inhibit the resorption of water and electrolytes in the renal tubules. However, such electrolyte-discharge type diuretics suffer from a problem in that they would essentially break the electrolyte balance in the living body (Aifred Goodman Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8.sup.th edition, pp.721-731, 1990) and therefore, there has recently been tried to develop so-called aquaresis which permit the selective excretion of only water.
The drugs possessing vasopressin receptor antagonism have attracted special interest recently, as drugs having aquaresis (Yamamura Yoshitaka et al., Br. J. Pharmacol., 1992, 105:787). In particular, there have been conducted various studies to develop vasopressin V2 receptor antagonists.
J.P. KOKAI No. Hei 7-2800 discloses certain benzamide derivatives, which possess vasopressin-receptor antagonism and are thus useful as medicines, in particular, vasodilators, aquaresis or the like. In these compounds, however, the hetero ring bonded to the carbonylphenyl carbamoyl group is not a tricyclic hetero ring.
P.I.A- No. WO95/03305 discloses that a fused benzazepine derivative characterized in that it has a chemical structure carrying a tricyclic heterocyclic benzazepine has vasopressin receptor antagonism and is effective as a medicine. This compound is recognized to have stronger and longer-lasting vasopressin V2 receptor antagonism as compared with OPC-31260 (P.I.A. No. WO91/05549) which is a vasopressin receptor antagonist presently in course of development. The compound has a chemical structure carrying a carbonylphenyl carbamoyl group, but the tricyclic hetero ring linked thereto is a benzazepine.
J.P. KOKAI No. 7-157486 discloses that a compound having a tricyclic diazepin ring possesses vasopressin receptor antagonism. However, this compound never has a biphenyl group.
Thus, the development of medicines possessing aquaresis has been made progress. Edema does not appear until pathema such as cancers from which many patients suffer, congestive heart failure, nephrotic syndromes and hepatocirrhosis are advanced to some extent. Since the patients suffering therefrom feel severe pains, there have intensively been desired for the development of novel compounds which have almost no side effect, highly efficient aquaresis, in particular, vasopressin receptor antagonism and are very useful, among clinicians.